Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials

Thumbnail Image
File version
Version of Record (VoR)
Burmester, Gerd R
Winthrop, Kevin
Blanco, Ricardo
Nash, Peter
Goupille, Philippe
Azevedo, Valderilio F
Salvarani, Carlo
Rubbert-Roth, Andrea
Lesser, Elizabeth
Lippe, Ralph
Lertratanakul, Apinya
Mccaskill, Reva M
Liu, John
Ruderman, Eric M
Griffith University Author(s)
Primary Supervisor
Other Supervisors
File type(s)

Introduction: This integrated analysis describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, at 15 and 30 mg once daily for up to 3 years of exposure in patients with active psoriatic arthritis (PsA) who had a prior inadequate response or intolerance to ≥ 1 non-biologic or biologic disease-modifying antirheumatic drug. Methods: Safety data were pooled and analyzed from two randomized, placebo-controlled phase 3 trials. Both trials evaluated upadacitinib 15 mg and 30 mg once daily, and one trial also evaluated adalimumab 40 mg every other week. Treatment-emergent adverse events (TEAEs) and laboratory data were summarized for four groups: pooled placebo, pooled upadacitinib 15 mg, pooled upadacitinib 30 mg, and adalimumab. TEAEs were reported as exposure-adjusted event rates (events per 100 patient-years [E/100 PY]) up to a data cut-off of June 29, 2020. Results: A total of 2257 patients received ≥ 1 dose of upadacitinib 15 mg (N = 907) or 30 mg (N = 921) for 2504.6 PY of exposure or adalimumab (N = 429) for 549.7 PY of exposure. Upper respiratory tract infection, nasopharyngitis, and increased creatine phosphokinase (CPK) were the most common TEAEs with upadacitinib. Rates of malignancies, adjudicated major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs), and deaths were similar across treatment groups. Rates of herpes zoster (HZ) and opportunistic infections (OI; excluding tuberculosis, HZ, and oral candidiasis) were higher with upadacitinib versus adalimumab. Serious infection, anemia, and CPK elevations were most frequent with upadacitinib 30 mg. Potentially clinically significant laboratory abnormalities were uncommon. Conclusions: Upadacitinib 15 mg and adalimumab had similar safety profiles with the exception of HZ and OIs, consistent with what was observed in rheumatoid arthritis. Rates of malignancies, MACEs, VTEs, and deaths were comparable among patients receiving upadacitinib and adalimumab. No new safety risks emerged with longer-term exposure to upadacitinib. Trial Registration Numbers: SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374.

Journal Title
Rheumatology and Therapy
Conference Title
Book Title
Thesis Type
Degree Program
Publisher link
Patent number
Grant identifier(s)
Rights Statement
© The Author(s) 2021. This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
Rights Statement
Item Access Status
Access the data
Related item(s)
Clinical pharmacology and therapeutics
Clinical sciences
Science & Technology
Life Sciences & Biomedicine
JAK inhibitor
Persistent link to this record
Burmester, GR; Winthrop, K; Blanco, R; Nash, P; Goupille, P; Azevedo, VF; Salvarani, C; Rubbert-Roth, A; Lesser, E; Lippe, R; Lertratanakul, A; Mccaskill, RM; Liu, J; Ruderman, EM, Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials, Rheumatology and Therapy, 2021, 9 (2), pp. 521-539